BACKGROUND: While family history (FHx) of prostate cancer (PCa) increases the risk of PCa, comparably less is known regarding the impact of FHx on pathologic and oncologic outcomes after radical prostatectomy (RP). METHODS: We retrospectively reviewed our multicenter database comprising 6,041 nonmetastatic PCa patients treated with RP. Patients with a FHx of PCa in one or more first-degree relatives were considered as FHx positive. We examined the association of FHx with pathologic outcomes and biochemical recurrence (BCR) using logistic and Cox regression models, respectively. RESULTS: In total, 1,677 (28%) patients reported a FHx of PCa. Compared to patients without FHx, those with, were younger at RP (median age of 59 vs. 62 years, p < 0.01), and had significantlymore favorable biopsy and RP histopathologic findings. On multivariable logistic regression analysis, positive FHx was associated with extracapsular extension (odds ratio [OR] 0.77, 95% confidence interval [CI] 0.66-0.90, p < 0.01; model AUC 0.73) and upgrading (OR 0.70, 95% CI 0.62-0.80, p < 0.01; model AUC 0.68). Incorporating FHx significantly improved the AUC of the base model for upgrading (p < 0.01). Positive FHx was not associated with BCR in pre- and postoperative multivariable models (p = 0.1 and p = 0.7); c-indexes of Cox multivariable models were: 0.73 and 0.82, respectively. CONCLUSIONS: We found that patients with clinically nonmetastatic PCa who have positive FHx of PCa undergo RP at a younger age and have more favorable pathologic outcomes. Nevertheless, FHx of PCa did not confer better BCR rates, suggesting that FHx leads to potentially early detection and treatment without impact on BCR.

Cancer Prognostics and Health Outcomes Unit University of Montreal Health Centre Montreal Canada

Department of Pathology Medical University of Vienna Vienna Austria

Department of Special Surgery Division of Urology Jordan University Hospital The University of Jordan Amman Jordan

Department of Urology 2nd Faculty of Medicine Charles University Prague Czech Republic

Department of Urology and Division of Experimental Oncology URI Urological Research Institute IRCCS San Raffaele Scientific Institute Milan Italy

Department of Urology Fudan University Shanghai Cancer Center Shanghai China

Department of Urology Jagiellonian University Krakow Poland

Department of Urology King Fahad Specialist Hospital Dammam Saudi Arabia

Department of Urology King Faisal Medical City Abha Saudi Arabia

Department of Urology Landesklinikum Wiener Neustadt Vienna Austria

Department of Urology Medical University of Silesia Zabrze Poland

Department of Urology Medical University of Vienna Vienna Austria

Department of Urology Okayama University Graduate School of Medicine Okayama Japan

Department of Urology Paracelsus Medical University Salzburg University Hospital Salzburg Salzburg Austria

Department of Urology San Giovanni Battista Hospital University of Turin Turin Italy

Department of Urology Semmelweis University Budapest Hungary

Department of Urology The Jikei University School of Medicine Tokyo Japan

Department of Urology University Medical Center Hamburg Eppendorf Hamburg Germany

Department of Urology University of Texas Southwestern Dallas TX USA

Department of Urology Weill Cornell Medical College New York NY USA

Division of Urology Hourani Center for Applied Scientific Research Al Ahliyya Amman University Amman Jordan

Institute for Urology and Reproductive Health Sechenov University Moscow Russia

Karl Landsteiner Institute of Urology and Andrology Vienna Austria

Men's Health and Reproductive Health Research Center Shahid Beheshti University of Medical Sciences Tehran Iran

Research Center for Evidence Based Medicine Tabriz University of Medical Sciences Tabriz Iran

See more in PubMed

Abdel-Rahman O. Prostate cancer incidence and mortality in relationship to family history of prostate cancer; findings from the PLCO trial. Clin Genitourin Cancer. 2019. Aug;17(4):e837–844. PubMed

Hemminki K. Familial risk and familial survival in prostate cancer. World J Urol. 2012. Apr;30(2):143–148. PubMed

Bratt O, Drevin L, Akre O, et al. Family history and probability of prostate cancer, differentiated by risk category: a nationwide population-based study. J Natl Cancer Inst. 2016. Oct;108(10):djw110. PubMed

Clements MB, Vertosick EA, Guerrios-Rivera L, et al. Defining the impact of family history on detection of high-grade prostate cancer in a large multi-institutional cohort. Eur Urol. 2021. Dec 31. PubMed PMC

Oh M, Alkhushaym N, Fallatah S, et al. The association of BRCA1 and BRCA2 mutations with prostate cancer risk, frequency, and mortality: a meta-analysis [article]. Prostate. 2019;79(8):880–895. PubMed

Zhen JT, Syed J, Nguyen KA, et al. Genetic testing for hereditary prostate cancer: current status and limitations [review]. Cancer. 2018;124(15):3105–3117. DOI:10.1002/cncr.31316 PubMed DOI

Mottet N, van den Bergh RCN, Briers E, et al. EAU-EANM-ESTRO-ESUR-SIOG guidelines on prostate cancer—2020 update. Part 1: screening, diagnosis, and local treatment with curative intent. Eur Urol. 2021;79(2):243–262. PubMed

Lughezzani G, Briganti A, Karakiewicz PI, et al. Predictive and prognostic models in radical prostatectomy candidates: a critical analysis of the literature. Eur Urol. 2010. Nov;58(5):687–700. PubMed PMC

Shariat SF, Kattan MW, Vickers AJ, et al. Critical review of prostate cancer predictive tools. Future Oncol. 2009. Dec;5(10):1555–1584. PubMed PMC

Cooperberg MR, Carroll PR. Trends in management for patients with localized prostate cancer, 1990-2013. JAMA. 2015. Jul 7;314(1):80–82. PubMed

Urabe F, Kimura S, Yamamoto S, et al. Impact of family history on oncological outcomes in primary therapy for localized prostate cancer patients: a systematic review and meta-analysis. Prostate Cancer Prostatic Dis. 2021. Sep;24(3):638–646. PubMed PMC

Spangler E, Zeigler-Johnson CM, Malkowicz SB, et al. Association of prostate cancer family history with histopathological and clinical characteristics of prostate tumors. Int J Cancer. 2005. Jan 20;113(3):471–474. PubMed

Westerman ME, Gershman B, Karnes RJ, et al. Impact of a family history of prostate cancer on clinicopathologic outcomes and survival following radical prostatectomy. World J Urol. 2016. Aug;34(8):1115–1122. PubMed

Roehl KA, Loeb S, Antenor JA, et al. Characteristics of patients with familial versus sporadic prostate cancer. J Urol. 2006. Dec;176(6 Pt 1):2438–2442. discussion 2442. PubMed

Thalgott M, Kron M, Brath JM, et al. Men with family history of prostate cancer have a higher risk of disease recurrence after radical prostatectomy. World J Urol. 2018. Feb;36(2):177–185. PubMed

Rajwa P, Schuettfort VM, D’andrea D, et al. Impact of systemic immune-inflammation index on oncologic outcomes in patients treated with radical prostatectomy for clinically nonmetastatic prostate cancer. Urol Oncol. 2021. Nov;39(11):e78519–78527. PubMed

Loeb S, Folkvaljon Y, Robinson D, et al. Evaluation of the 2015 Gleason grade groups in a nationwide population-based cohort. Eur Urol. 2016. Jun;69(6):1135–1141. PubMed PMC

Gallina A, Chun FK, Suardi N, et al. Comparison of stage migration patterns between Europe and the USA: an analysis of 11 350 men treated with radical prostatectomy for prostate cancer. BJU Int. 2008. Jun;101(12):1513–1518. PubMed

Shariat SF, Anwuri VA, Lamb DJ, et al. Association of preoperative plasma levels of vascular endothelial growth factor and soluble vascular cell adhesion molecule-1 with lymph node status and biochemical progression after radical prostatectomy. J Clin Oncol. 2004. May 1;22(9):1655–1663. PubMed

Xylinas E, Rink M, Robinson BD, et al. Impact of histological variants on oncological outcomes of patients with urothelial carcinoma of the bladder treated with radical cystectomy. Eur J Cancer. 2013. May;49(8):1889–1897. PubMed

Nyberg T, Frost D, Barrowdale D, et al. Prostate cancer risks for male BRCA1 and BRCA2 mutation carriers: a prospective cohort study. Eur Urol. 2020. Jan;77(1):24–35. PubMed PMC

Page EC, Bancroft EK, Brook MN, et al. Interim results from the IMPACT study: evidence for prostate-specific antigen screening in BRCA2 mutation carriers. Eur Urol. 2019. Dec;76(6):831–842. PubMed PMC

Gandaglia G, Briganti A, Montorsi F. Reimagining prostate cancer screening: the IMPACT of germline mutations. Lancet Oncol. 2021;22(11):1491–1492. PubMed

Kasivisvanathan V, Rannikko AS, Borghi M, et al. MRI-targeted or standard biopsy for prostate-cancer diagnosis. N Engl J Med. 2018. May 10;378(19):1767–1777. PubMed PMC

Rajwa P, Pradere B, Quhal F, et al. Reliability of serial prostate magnetic resonance imaging to detect prostate cancer progression during active surveillance: a systematic review and meta-analysis. Eur Urol. 2021. Nov;80(5):549–563. PubMed

Rajwa P, Mori K, Huebner NA, et al. The prognostic association of prostate MRI PI-RADS™ v2 assessment category and risk of biochemical recurrence after definitive local therapy for prostate cancer: a systematic review and meta-analysis. J Urol. 2021. Sep;206(3):507–516. PubMed

Schneider A, Bowler N, Fogg R, et al. The impact of a positive family history on clinical and pathologic outcomes of active surveillance for prostate cancer. J Clin Oncol. 2021;39(6_suppl):225-225. 2021/02/20. DOI:10.1200/JCO.2021.39.6_suppl.225 DOI

Halstuch D, Ber Y, Kedar D, et al. Short-term outcomes of active surveillance for low risk prostate cancer among men with germline DNA repair gene mutations [article]. J Urol. 2020;204(4):707–713. DOI:10.1097/JU.0000000000001027 PubMed DOI

Carter HB, Helfand B, Mamawala M, et al. Germline mutations in ATM and BRCA1/2 are associated with grade reclassification in men on active surveillance for prostate cancer. Eur Urol. 2019. May;75(5):743–749. PubMed PMC

Castro E, Goh C, Olmos D, et al. Germline BRCA mutations are associated with higher risk of nodal involvement, distant metastasis, and poor survival outcomes in prostate cancer [article]. J Clin Oncol. 2013;31(14):1748–1757. DOI:10.1200/JCO.2012.43.1882 PubMed DOI PMC

Allemailem KS, Almatroudi A, Alrumaihi F, et al. Single nucleotide polymorphisms (SNPs) in prostate cancer: its implications in diagnostics and therapeutics. Am J Transl Res. 2021;13(4):3868–3889. PubMed PMC

den Broeck T V, Joniau S, Clinckemalie L, et al. The role of single nucleotide polymorphisms in predicting prostate cancer risk and therapeutic decision making. BioMed Res Int. 2014;2014:627510. PubMed PMC